Abstract 9760: Plasma Levels of Nitric Oxide Metabolites Are Markedly Reduced In Normotensive Individuals With Electrocardiographically Determined Left Ventricular Hypertrophy

Abstract

Objective: It has recently been revealed that normotensive subjects with electrocardiographically determined left ventricular hypertrophy (ECG-LVH) are at risk of multiple cardiovascular diseases, but the underlying mechanism remains to be elucidated. To address this point, we examined the hypothesis that normotensive individuals with ECG-LVH show reduced plasma levels of metabolites of nitric oxide (NO), a critical regulator of cardiovascular function. Methods: A total of 579 Japanese male workers (40-65 years of age) were studied. Since hypertension (blood pressure ≥140/90 mmHg) or medications could influence plasma NOx (NO metabolites, nitrite and nitrate), workers with such factors were excluded from the study. ECG-LVH was assessed by the Sokolow-Lyon voltage criteria and the Cornell voltage-duration product. The subjects were categorized by quartiles of plasma NOx level, and a multivariate logistic regression analysis was conducted relating ECG-LVH to NOx quartiles after adjustment for potential confounders. Results: The mean levels of plasma NOx were markedly lower in individuals with ECG-LVH (n=73, 28.9±19.2 μ mol/l) than in those without (n=506, 42.5±31.2 μ mol/l) ( P <0.0001). The multivariate-adjusted odd ratio for the presence of ECG-LVH compared with the forth quartile of NOx (≥51.9 μ mol/l) was 1.38 (95% CI 0.55-3.59) for the third (NOx 33.1-51.8 μ mol/l), 1.83 (0.76-4.64) for the second (NOx 21.3-33.0 μ mol/l) and 4.93 (2.31-11.47) for the first quartile (NOx ≤21.2 μ mol/l). Similar result was obtained when subjects were stratified by waist circumference. The mean levels of plasma extracellular superoxide dismutase (EC-SOD), a major antioxidant in the cardiovascular system, were comparable in individuals with and without ECG-LVH. On the other hand, plasma EC-SOD levels were significantly decreased with lower quartiles of NOx ( P <0.01). Conclusion: This study demonstrated for the first time that plasma NOx levels are markedly reduced in normotensive individuals with ECG-LVH. These results indicate that disrupted NO production through the involvement of down-regulation of the antioxidant enzyme may explain, at least in part, the potential mechanism for increased cardiovascular risk in normotensive individuals with ECG-LVH.